An On/Off Switch for Sex and Violence

Now that the biologists had identified one site—out of many—housing neurons that activated selectively for social encounters, they listened in on the goings-on by placing very fine electrodes in proximity. Silent when the mouse is solitary, these cells’ activity level progressively increased as a male intruder entered the cage and the resident mouse attacked. More puzzling was the observation that some neurons were also active, albeit only transiently, in the initial exploratory phases of mating with a female. Conversely, many of the cells signaling during fighting were actively suppressed during mating, indicating an inherent opposition between aggression and sex. To paraphrase the 1960s slogan: you either make love or war, but not both.

So far these experiments have revealed interesting correlations between ­neuronal activity and behavior (fighting). But what role does VMHvl play in aggression? Are its neurons the cause of fighting?

Marrying Light and Genes
Anderson and his team are masters at exploiting a remarkable technique known as optogenetics [see “Playing the Body Electric,” Consciousness Redux; March/April 2010] to stimulate hundreds to perhaps thousands of cells in the VMHvl, out of the 40 million cells of the mouse brain. Scientists injected into the VMHvl on one side of the animal stunted viruses carrying a modified piece of DNA engineered to encode a photosensitive ion channel selective to blue light. Because it is dark in the catacombs of the brain, enlightenment comes from a tiny optical fiber snaking its way through the tissue. Expressed in the membrane separating the cell from the outside, the neuron responded to blue light with excitation. Every pulse of light reliably triggered one or more electrical pulses in the infected neuron. Once the animals recovered, little difference was apparent in their behavior alone or when interacting with another.

Stimulating the VMHvl when the mouse was by itself did not do anything. Yet in the presence of another animal, the mouse initiated a concerted attack, often by biting the back of the intruder. Unusually for this species, the illuminated male indiscriminately attacked female, castrated male or anesthetized mice—and sometimes even a blown-up latex glove. Aggression ceased once the light stopped. The infection and light delivery had to be targeted to the VMHvl nucleus; stimulating nearby regions did not produce such an effect. It is a striking and immediate demonstration of the link between neurons and behavior. Exciting VMHvl neurons causes aggression.

Finally, Anderson and his team turned to the question of whether the VMHvl cells are necessary for aggression to occur. Using a different technique, they genetically “silenced” VMHvl cells, turning them effectively off for days at a time. This silencing significantly reduced the chances of an aggressive encounter and lengthened the time it took to initiate an attack.

Of course, we do not know what the infected rodent experiences in its murine mind when light beams illuminate its hypothalamic attack center. But its behavior is fully compatible with the idea that its sudden violence is accompanied by a bout of petulant anger directed at anything nearby, including helpless victims that pose no threat. Some readers may not be strangers to such “irrational” impulsive feelings welling up. But fortunately, most of us can control our anger, not lashing out at our screaming boss, possibly by inhibiting our hypothalamus via descending fibers from the prefrontal cortex. It is not unreasonable to hope that researchers can investigate the neuronal basis of such anger management in the mouse in the near future.

ABOUT THE AUTHOR(S)

CHRISTOF KOCH is chief scientific officer at the Allen Institute for Brain Science in Seattle and Lois and Victor Troendle Professor of Cog­nitive and Behavioral Biology at the Cal­ifornia Institute of Technology. He serves on Scientific American Mind's board of advisers.